Racemic oxybutynin is used therapeutically in the treatment of intestinal hypermotility and in the treatment of urinary incontinence due to detrusor instability. Racemic oxybutynin exerts a direct antispasmodic effect on smooth muscle and inhibits the action of acetylcholine on smooth muscle. It exhibits only one-fifth of the anticholinergic activity of atropine on the rabbit detrusor muscle, but four to ten times the antispasmodic activity. It is quite selective for muscarinic receptors in the presence of nicotinic receptors and as a result, no blocking effects are observed at skeletal neuromuscular junctions or autonomic ganglia.
Racemic oxybutynin relaxes bladder smooth muscle and, in patients with conditions characterized by involuntary bladder contractions, cystometric studies have demonstrated that racemic oxybutynin increases vesicle capacity, diminishes the frequency of involuntary contractions of the detrusor muscle, and delays the initial desire to void. It is therefore useful in the treatment and prevention of both incontinency and frequent voluntary urination. The efficacy of racemic oxybutynin in the bladder has been attributed to a combination of antimuscarinic, direct spasmolytic and local anesthetic effects on the detrusor smooth muscle. Because of the antimuscarinic activity of the racemic drug, xerostomia (dry mouth) and mydriasis (dilated pupils), which involve muscarinic cholinergic receptors, are very common side effects. In fact, at least one researcher has referred to the "inevitable symptoms of mydriasis, xerostomia, tachycardia, etc." that accompany the administration of racemic oxybutynin [Lish et al. Arch. Int. Pharmacodyn. 156, 467-488 (1965), 481]. The high incidence of anticholinergic side effects (40 to 80%) often results in dosage reduction or discontinuation of therapy.
Pharmacological studies of the individual enantiomers have suggested that the R-enantiomer is the efficacious enantiomer. Noronha-Blob et al. [J. Pharmacol. Exp. Ther. 256, 562-567 (1991)] concluded that the cholinergic antagonism of racemic oxybutynin (measured in vitro by its affinity for M.sub.1, M.sub.2 and M.sub.3 receptors subtypes and in vivo for diverse physiological responses) could be attributed mainly to the activity of the R-enantiomer. For all responses they found the rank order of potency of racemic oxybutynin and its enantiomers to be the same, namely, (R)-oxybutynin greater than or equal to racemic oxybutynin, which was much greater than (S)-oxybutynin, with (S)-oxybutynin being 1 to 2 orders of magnitude less potent than (R)-oxybutynin.